This proposal seeks funding to continue a nationally competitive biomedical research center in North Dakota State University focused on the study of proteases in disease. The Center for Protease Research was established in 2001 with funds from the COBRE program. It is currently in its sixth year of funding. The previous grant application had a strong focus on chemistry while this renewal application will have a strong biology component with cancer and asthma as the primary disease targets. Understanding the biological role played by matrix metalloproteinases and histone deacetylases in cancer and other diseases such as asthma will be a major scientific goal. The Center will coordinate the expertise of five new investigators: Gregory Cook, Glenn Dorsam, Emilio Esposito, Department of Chemistry and Molecular Biology, Bin Guo, Department of Pharmaceutical Sciences and Jane Schuh, Department of Veterinary and Microbiological Sciences. A senior faculty member with expertise in the biology area, and experience to mentor the junior faculty members, will be recruited in the first year of the proposed grant period. Core facilities in biology and synthetic chemistry will play a key role in assisting the research programs of the new Pis, research programs that were initiated during the previous grant period, other NDSU researchers, and North Dakota INBRE researchers. The COBRE Center will continue to build infrastructure, initiate new activities, and continue successful previous programs to foster growth of biomedical research in North Dakota. Combating cancer, one of the leading causes of mortality in humans, is a major goal for biomedical scientists. The NDSU-COBRE center will conduct research to provide fundamental information on how proteases, a key biological player in several diseases, impacts cancer. These studies have the potential to provide novel therapeutics that can treat this deadly disease.